Pharmacology Biochemistry and Behavior最新文献

{"title":"Differentially regulated targets in the fast-acting antidepressant effect of (R)-ketamine: A systems biology approach","authors":"Ellen Scotton ,&nbsp;Pedro Lenz Casa ,&nbsp;Fernanda Pessi de Abreu ,&nbsp;Scheila de Avila e Silva ,&nbsp;Renata Luiza Boff Wilges ,&nbsp;Marcos Vinicius Rossetto ,&nbsp;Luiza Paul Géa ,&nbsp;Adriane R. Rosa ,&nbsp;Rafael Colombo","doi":"10.1016/j.pbb.2023.173523","DOIUrl":"10.1016/j.pbb.2023.173523","url":null,"abstract":"<div><p><span><span><span>Approximately two-thirds of patients with major depressive disorder (MDD) fail to respond to conventional antidepressants, suggesting that additional mechanisms are involved in the MDD pathophysiology. In this scenario, the </span>glutamatergic system represents a promising therapeutic target for treatment-resistant depression. To our knowledge, this is the first study using semantic approach with systems biology to identify potential targets involved in the fast-acting </span>antidepressant effects<span><span> of ketamine and its </span>enantiomers as well as identifying specific targets of (</span></span><em>R</em><span>)-ketamine. We performed a systematic review, followed by a semantic analysis and functional gene enrichment to identify the main biological processes involved in the therapeutic effects of these agents. Protein-protein interaction networks were constructed, and the genes exclusively regulated by (</span><em>R</em>)-ketamine were explored. We found that the regulation of α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid (AMPA) receptor and <em>N</em>-methyl-<span>d</span><span><span>-aspartate (NMDA) receptor subunits–Postsynaptic Protein 95 (PSD-95), Brain Derived Neurotrophic Factor (BDNF), and </span>Tyrosine<span><span> Receptor Kinase B (TrkB) are shared by the three-antidepressant agents, reinforcing the central role of the glutamatergic system and neurogenesis<span> on its therapeutic effects. Differential regulation of Transforming Growth Factor Beta 1 (TGF-β1) receptors–Mitogen-Activated Protein Kinases (MAPK's), Receptor Activator of Nuclear Factor-Kappa Beta Ligand (RANKL), and </span></span>Serotonin Transporter (SERT) seems to be particularly involved in (</span></span><em>R</em>)-ketamine antidepressant effects. Our data helps further studies investigating the relationship between these targets and the mechanisms of (<em>R</em>)-ketamine and searching for other therapeutic compounds that share the regulation of these specific biomolecules. Ultimately, this study could contribute to improve the fast management of depressive-like symptoms with less detrimental side effects than ketamine and (<em>S</em>)-ketamine.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"223 ","pages":"Article 173523"},"PeriodicalIF":3.6,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9706046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of group II metabotropic glutamate receptors in ketamine's antidepressant actions","authors":"Anna Onisiforou ,&nbsp;Polymnia Georgiou ,&nbsp;Panos Zanos","doi":"10.1016/j.pbb.2023.173531","DOIUrl":"10.1016/j.pbb.2023.173531","url":null,"abstract":"<div><p><span>Major Depressive Disorder (MDD) is a serious neuropsychiatric disorder afflicting around 16–17 % of the global population and is accompanied by recurrent episodes of low mood, hopelessness and suicidal thoughts. Current pharmacological interventions take several weeks to even months for an improvement in depressive symptoms to emerge, with a significant percentage of individuals not responding to these medications at all, thus highlighting the need for rapid and effective next-generation treatments for MDD. Pre-clinical studies in animals have demonstrated that antagonists of the metabotropic glutamate receptor subtype 2/3 (mGlu</span>_2/3<span> receptor) exert rapid antidepressant-like effects, comparable to the actions of ketamine. Therefore, it is possible that mGlu</span>₂ or mGlu₃ receptors to have a regulatory role on the unique antidepressant properties of ketamine, or that convergent intracellular mechanisms exist between mGlu_2/3<span> receptor signaling and ketamine's effects. Here, we provide a comprehensive and critical evaluation of the literature on these convergent processes underlying the antidepressant action of mGlu</span>_2/3 receptor inhibitors and ketamine. Importantly, combining sub-threshold doses of mGlu_2/3 receptor inhibitors with sub-antidepressant ketamine doses induce synergistic antidepressant-relevant behavioral effects. We review the evidence supporting these combinatorial effects since sub-effective dosages of mGlu_2/3<span><span> receptor antagonists and ketamine could reduce the risk for the emergence of significant adverse events compared with taking normal dosages. Overall, </span>deconvolution of ketamine's pharmacological targets will give critical insights to influence the development of next-generation antidepressant treatments with rapid actions.</span></p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"223 ","pages":"Article 173531"},"PeriodicalIF":3.6,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9329515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adolescent intermittent ethanol exposure enhances adult stress effects in male rats","authors":"Kati L. Healey,&nbsp;Sandra Kibble,&nbsp;Kira Dubester,&nbsp;Amelia Bell,&nbsp;H.S. Swartzwelder","doi":"10.1016/j.pbb.2022.173513","DOIUrl":"10.1016/j.pbb.2022.173513","url":null,"abstract":"<div><p><span><span>Binge patterns of alcohol use, prevalent among adolescents, are associated with a higher probability of developing alcohol use disorders (AUD) and other psychiatric disorders, like anxiety and depression. Additionally, adverse life events strongly predict AUD and other psychiatric disorders. As such, the combined fields of stress and AUD have been well established, and animal models indicate that both binge-like alcohol exposure and stress exposure elevate anxiety-like </span>behaviors<span>. However, few have investigated the interaction of adolescent intermittent ethanol (AIE) and adult stressors. We hypothesized that AIE would increase vulnerability to restraint-induced stress (RS), manifested as increased anxiety-like behavior. After AIE exposure, in adulthood, animals were tested on forced swim (FST) and saccharin preference (SP) and then exposed to either RS (90 min/5 days) or home-cage control. Twenty-four hours after the last RS session, animals began testing on the elevated plus maze<span><span> (EPM), and were re-tested on FST and SP. A separate group of animals were sacrificed in adulthood after AIE and RS, and brains were harvested for </span>immunoblot<span> analysis of dorsal and ventral hippocampus. Consistent with previous reports, AIE had no significant effect on closed arm time in the EPM (anxiety-like behavior). However, in male rats the interaction of AIE and adult RS increased time spent in the closed arms. No effect was observed among female animals. AIE and RS-specific alterations were found in glial and synaptic markers (GLT-1, </span></span></span></span>FMRP and PSD-95) in male animals. These findings indicate AIE has sex-specific effects on both SP and the interaction of AIE and adult RS, which induces a propensity toward anxiety-like behavior in males. Also, AIE produces persistent hippocampal deficits that may interact with adult RS to cause increased anxiety-like behaviors. Understanding the mechanisms behind this AIE-induced increase in stress vulnerability may provide insight into treatment and prevention strategies for alcohol use disorders.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"223 ","pages":"Article 173513"},"PeriodicalIF":3.6,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10028459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9335978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The antidepressant agomelatine attenuates morphine-induced reinstatement but not self-administration or precipitated withdrawal","authors":"Alok De ,&nbsp;Ken W. Grasing","doi":"10.1016/j.pbb.2023.173525","DOIUrl":"10.1016/j.pbb.2023.173525","url":null,"abstract":"<div><h3>Background</h3><p>Exogenous melatonin<span> appears to have anti-addictive properties and was recently shown to improve mental health and metabolic measures in patients receiving chronic opioid maintenance therapy. Agomelatine<span> is a marketed antidepressant which acts as a melatonin agonist. We evaluated its effects using a rat model of morphine-reinforced behavior.</span></span></p></div><div><h3>Methods</h3><p>After pretreatment with noncontingent morphine, male Wistar rats were trained to self-administer intravenous morphine (1.0 mg/kg-injection) under a progressive-ratio schedule. Rats were pretreated with vehicle or agomelatine during extinction, reinstatement, and reacquisition of morphine-reinforced behavior.</p></div><div><h3>Results</h3><p>Daily treatment with 10 mg/kg-day of agomelatine decreased the number of ratios completed and prolonged latency during morphine-induced reinstatement. There were no significant effects on cue-induced reinstatement, morphine self-administration, or naloxone-precipitated withdrawal. Treatment with 32 mg/kg-day of agomelatine caused postural changes. That dose prolonged withdrawal-induced loss of body weight and caused delayed reductions in food reinforcement.</p></div><div><h3>Summary</h3><p>In addition to postural effects, high-dose agomelatine worsened the course of spontaneous withdrawal and produced nonspecific effects on food-reinforced behavior. When administered at a selective dose, agomelatine did not modify morphine self-administration or precipitated withdrawal, but decreased morphine-induced reinstatement. Our findings show potential detrimental effects of high-dose agomelatine, with reductions in opioid-seeking behavior after a lower, more selective dose.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"223 ","pages":"Article 173525"},"PeriodicalIF":3.6,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10429619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholesterol metabolism pathway in autism spectrum disorder: From animal models to clinical observations","authors":"Jaime Lin ,&nbsp;Victória Linden de Rezende ,&nbsp;Maiara de Aguiar da Costa ,&nbsp;Jade de Oliveira ,&nbsp;Cinara Ludvig Gonçalves","doi":"10.1016/j.pbb.2023.173522","DOIUrl":"10.1016/j.pbb.2023.173522","url":null,"abstract":"<div><p><span><span><span><span>Autism Spectrum Disorder (ASD) is a </span>neurodevelopmental disorder characterized by a persistent impairment of social skills, including aspects of perception, interpretation, and response, combined with restricted and </span>repetitive behavior. ASD is a complex and multifactorial condition, and its etiology could be attributed to </span>genetic<span><span> and environmental factors. Despite numerous clinical and experimental studies, no etiological factor, biomarker, and specific model of transmission have been consistently associated with ASD. However, an imbalance in cholesterol levels has been observed in many patients, more specifically, a condition of hypocholesterolemia, which seems to be shared between ASD and ASD-related genetic syndromes such as </span>fragile X syndrome (FXS), </span></span>Rett syndrome<span><span> (RS), and Smith- Lemli-Opitz (SLO). Furthermore, it is known that alterations in cholesterol levels lead to neuroinflammation<span>, oxidative stress, impaired </span></span>myelination<span><span> and synaptogenesis. Thus, the aim of this review is to discuss the cholesterol metabolic pathways in the ASD context, as well as in genetic syndromes related to ASD, through clinical observations and </span>animal models<span>. In fact, SLO, FXS, and RS patients display early behavioral markers of ASD followed by cholesterol disturbances. Several studies have demonstrated the role of cholesterol in psychiatric conditions<span><span> and how its levels modulate brain neurodevelopment<span>. This review suggests an important relationship between ASD pathology and cholesterol metabolism impairment; thus, some strategies could be raised – at clinical and pre-clinical levels – to explore whether cholesterol metabolism disturbance has a generally </span></span>adverse effect in exacerbating the symptoms of ASD patients.</span></span></span></span></p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"223 ","pages":"Article 173522"},"PeriodicalIF":3.6,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9542896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in serotonergic control of rat social behaviour","authors":"Ieva Poceviciute,&nbsp;Kamile Kasperaviciute,&nbsp;Rokas Buisas,&nbsp;Osvaldas Ruksenas,&nbsp;Valentina Vengeliene","doi":"10.1016/j.pbb.2023.173533","DOIUrl":"10.1016/j.pbb.2023.173533","url":null,"abstract":"<div><h3>Rationale</h3><p>There is increasing evidence that enhancement of the salience of social stimuli can have a beneficial effect in managing many psychiatric conditions. There are, however, clear sex-related differences in social behaviour, including the neural mechanisms responsible for different aspects of social functions.</p></div><div><h3>Objectives</h3><p>We explored the role of the serotonergic system on rat social behaviour under baseline and under stressful conditions in female and male rats.</p></div><div><h3>Methods</h3><p><span>Rats were treated with the selective serotonin transporter<span> (SERT) inhibitor escitalopram postnatally; a procedure known to cause a long-lasting reduction of serotonergic activity. In adulthood, social behaviour was tested in a </span></span>social interaction<span> test and in ultrasonic vocalisation (USVs) recording sessions before and after yohimbine-induced stress-like state.</span></p></div><div><h3>Results</h3><p>Our data demonstrated that both female and, to a lesser extent, male escitalopram treated rats, exposed to a novel social situation, had fewer social exploration events and emitted fewer frequency-modulated calls with trills, trills and step calls, suggesting that an impaired function of the serotonergic system reduced the positive valence of social interaction. In a stress-like state, 50 kHz flat calls were increased only in female rats, indicating an increased seeking of social contact. However, the number of flat calls in escitalopram treated female rats was significantly lower compared with control rats.</p></div><div><h3>Conclusions</h3><p>These data suggest that females may respond differently to serotonergic pharmacotherapy with respect to enhancement of beneficial effects of social support, especially in stress-related situations.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"223 ","pages":"Article 173533"},"PeriodicalIF":3.6,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9336499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential patterns of opioid and dopamine D1 receptor antagonism on nutritive and non-nutritive sweetener intakes in C57BL/6:129 hybrid mice relative to inbred C57BL/6 and 129 mice","authors":"Matthew Roland ,&nbsp;Eli Berglas ,&nbsp;Rachel Pines ,&nbsp;Ion Carata ,&nbsp;Alexander Castillo ,&nbsp;Mirna Nashed ,&nbsp;Anthony Sclafani ,&nbsp;Richard J. Bodnar","doi":"10.1016/j.pbb.2023.173514","DOIUrl":"10.1016/j.pbb.2023.173514","url":null,"abstract":"<div><p><span><span>Opioid and dopamine (DA) D1 receptor antagonists differentially reduce nutritive and non-nutritive sweetener intakes in </span>inbred mouse strains<span>. Sucrose intake was more effectively reduced by </span></span>naltrexone<span> in C57BL/6 (B6) mice relative to 129P3<span><span> (129) mice, but more effectively reduced by SCH23390 in 129 mice<span> relative to B6 mice. Opioid and </span></span>DA D1 antagonists<span> differentially reduced saccharin intakes in B6 mice relative to other strains. Given these differential patterns in sweetener intake in B6 and 129 mice, the present study examined whether systemic naltrexone (0.01–5 mg/kg) and SCH23390 (50–1600 nmol/kg) reduced intakes of 10 % sucrose or 0.2 % saccharin solutions over a 120 min time course in first-generation hybrid mice (B6:129) of B6 and 129 parents and reduced low-nutritive sweetener intakes in 129 mice. Naltrexone (5 mg/kg) significantly reduced 10 % sucrose intake in B6:129 hybrid mice more like that of 129 than B6 mice. In contrast, SCH23390 (400–1600 nmol/kg) reduced 10 % sucrose intake in B6:129 hybrid mice more effectively than that observed in B6 or 129 parental strains. Because 129 mice consumed relatively low amounts of 0.2 % saccharin, they were tested with a more attractive low-nutritive solution containing 0.2 % saccharin and 2 % sucrose. Naltrexone failed to reduce saccharin intake in B6:129 hybrid mice but suppressed saccharin+sucrose intake in 129 mice more like that observed in B6 mice. SCH23390 similarly inhibited saccharin or saccharin+sucrose intakes in hybrid B6:129, 129, and B6 mice with B6 mice more resistant to the lowest SCH23390 dose. Thus, whereas sucrose intake in B6:129 hybrid mice exhibited similar sensitivity to opioid and to a lesser degree DA D1 antagonism to their 129, but not B6 parents, opioid and DA D1 mediation of low- and non-nutritive sweet intake produced unique profiles among B6:129 hybrid and B6 and 129 strains which does not support a simple heritability explanation.</span></span></span></p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"223 ","pages":"Article 173514"},"PeriodicalIF":3.6,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9341141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-weaning social isolation increases the incentive value of nicotine-related contexts and decreases the accumulation of ΔFosB in nucleus accumbens in adolescent rats","authors":"Diana M. Cortés-Patiño,&nbsp;Hans Ballesteros-Acosta,&nbsp;Valentyna Martin Neira,&nbsp;David Rikardo Pérez Contreras,&nbsp;Marisol R. Lamprea","doi":"10.1016/j.pbb.2023.173529","DOIUrl":"10.1016/j.pbb.2023.173529","url":null,"abstract":"<div><p>Adolescent social conditions profoundly affect vulnerability to drug abuse. Preclinical studies have shown that preventing social interactions during adolescence increases the rewarding effects of drugs like alcohol, cocaine, or amphetamines, however, little data exist regarding the impact of social isolation on nicotine effects. The current study evaluated the effects of differential rearing conditions during adolescence (isolation or group rearing) on (1) conditioned place preference induced by low nicotine doses (0.1 or 0.3 mg/kg) and (2) sensitization to the locomotor effects of nicotine after sub-chronic administration (3) and accumulation of <em>ΔFosB</em> in nucleus accumbens (NAc). Results showed that nicotine induced place preference in isolated and grouped rats, but the effect was more persistent for the rats reared in isolation. Isolated reared rats also exhibited lower levels of <em>ΔFosB</em> accumulation in NAc. No differences were found in the behavioral sensitization to nicotine effects between rearing conditions. The results suggest that isolation engenders a more robust incentive value of nicotine-related contexts. This effect could be related to the basal expression of ΔFosB: lower levels of this transcription factor seem to impair the motivation of isolated reared rats and increase their vulnerability to the effects of drugs like nicotine.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"223 ","pages":"Article 173529"},"PeriodicalIF":3.6,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9337112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blocking the ErbB pathway during adolescence affects the induction of anxiety-like behavior in young adult maternal immune activation offspring","authors":"Saher Abu-Ata ,&nbsp;Orya Noa Shukha ,&nbsp;Yaseen Awad-Igbaria ,&nbsp;Karen Ginat ,&nbsp;Eilam Palzur ,&nbsp;Idit Golani ,&nbsp;Alon Shamir","doi":"10.1016/j.pbb.2022.173497","DOIUrl":"10.1016/j.pbb.2022.173497","url":null,"abstract":"<div><p><span><span><span><span>Epidemiological and experimental evidence demonstrates that maternal exposure to infection during gestation increases the offspring's risk of developing schizophrenia and other neurodevelopmental disorders. In addition, the NRG-ErbB4 </span>signaling pathway<span><span> is involved in brain development and neuropsychiatric disorders. Specifically, this pathway modulates the dopaminergic and GABAergic systems and is expressed in the early stages of </span>prenatal development. We recently demonstrated that maternal immune activation (MIA) at late gestation altered the expression of NRG1, its </span></span>receptor ErbB4, and the </span>dopamine D2 receptor<span> four hours post-injection of viral or LPS in the fetal brain. We also reported that blocking the ErbB pathway during adolescence resulted in increased striatal DA content and reduced preference for sweetness and alcohol that persists into adulthood. However, the combined effects of MIA, re-activation of the immune system, and disruption of the ErbB signaling during adolescence would affect young adult mice's behavioral phenotype is unknown. Here, we report that the expression levels of the NRG1, ErbB4, GAD</span></span>₆₇<span><span><span>, and BDNF were changed as responses to MIA and blocked the ErbB signaling in the frontal cortex of adolescent mice. MIA-Offspring during late gestation and immune system re-activation during adolescence spent less time in the open arms of the elevated plus-maze in adulthood. At the same time, MIA-offspring administrated with the pan-ErbB inhibitor during adolescence spent the same amount of time in the opened arm as the control mice. Combining the ErbB signaling disruption during adolescence leads to a </span>social interaction impairment in female offspring, but not male, without affecting the offspring's motor activity, long-term recognition, and working memory. These results imply that blocking the ErbB signaling during adolescence prevents the development of anxiety-like </span>behavior of the MIA offspring later in life and suggest that this interaction does not reduce the risk of female MIA offspring developing impaired social behavior.</span></p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"222 ","pages":"Article 173497"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9206445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mirtazapine attenuates the cocaine-induced locomotor sensitization in male and female C57BL/6J and BALBA/cJ mouse","authors":"Susana Barbosa Méndez,&nbsp;Alberto Salazar-Juárez","doi":"10.1016/j.pbb.2022.173507","DOIUrl":"10.1016/j.pbb.2022.173507","url":null,"abstract":"<div><h3>Background</h3><p><span>Clinical studies have described the efficacy of various therapeutic approaches. Results are inconsistent and clinical application is limited. Clinical trials<span><span> have suggested that individual variability in the response to pharmacological therapies and sex affects the efficacy of some antidepressant drugs. Mouse strain-dependent variability influenced the response to antidepressant drugs. Some mouse strains respond faster and better to antidepressants than other mouse strains. We recently reported a series of </span>preclinical studies<span> that showed that dosing of mirtazapine, a noradrenergic and </span></span></span>serotonergic<span> antidepressant, in male and female Wistar rats decreased cocaine-induced locomotor activity and attenuated the induction and expression of cocaine-induced locomotor sensitization. Therefore, the aim of this study was to evaluate the mirtazapine effects, on cocaine-induced locomotor activity and cocaine-induced locomotor sensitization in male and female mice of the C57BL/6J and BALB/cJ strains, which differ in sensitivity to the cocaine motor effects and response to antidepressant drugs.</span></p></div><div><h3>Methods</h3><p>Male and female BALB/cJ and C57BL/6J inbred mice<span> (20–25 g) were daily dosed with 10 mg/kg of cocaine during the induction and expression of locomotor sensitization. During drug withdrawal, cocaine was withdrawn, and the groups received daily mirtazapine (30 mg/kg, i.p.) or saline. Mirtazapine was administered 30 min before cocaine. After each administration, locomotor activity for each animal was recorded for 30 min in transparent Plexiglass activity chambers.</span></p></div><div><h3>Results</h3><p>Cocaine-induced locomotor activity were greater in C57BL/6J strain mice than BALB/cJ strain mice during the induction and expression phase of locomotor sensitization. The female mice of both strains showed a higher cocaine locomotor response than males and mirtazapine significantly decreased cocaine-induced locomotor activity, as well as the induction and expression of locomotor sensitization, regardless of mouse strain or sex.</p></div><div><h3>Conclusion</h3><p>The results suggest mirtazapine may be considered an effective therapeutic option to treat cocaine use disorder in men and women with very diverse genetic backgrounds.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"222 ","pages":"Article 173507"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10637541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}